Bioabsorbable Sealant

ABSTRACT

Abstract of Disclosure 
     Openings in a mammalian body made by any medical procedure or non-medical event are sealed with a bioabsorbable plug or sewn with a bioabsorbable suture. In one exemplary embodiment, the plug in dehydrated, unexpanded condition is pushed by a pushing device through the lumen of a needle until a first part of the plug is external to the opening and a second part is internal to the opening. The needle is then withdrawn while the position of the pushing device is maintained. The pushing device is then withdrawn, leaving the plug in sealing relation to the opening. The body&#39;s moisture causes the plug to expand to complete the sealing of the opening, or the expansion may be caused by exposure to air, light, or other stimulant. The opening may be formed in soft tissue, internal organs, or hard tissue. The plug seals the flow of liquid or gaseous biological fluids.

Background of Invention

[0001] CROSS-REFERENCE TO RELATED DISCLOSURES

[0002] This disclosure is a divisional application claiming the benefitof the filing date of pending U.S. patent application entitled:"Bioabsorbable Sealant," by the same inventor, filed on December 7,2001, bearing Serial No. 09/683,282.

[0003] BACKGROUND OF THE INVENTION

[0004] Field of the invention

[0005] This invention relates, generally, to the medical arts. Moreparticularly, it relates to means for sealing openings in a mammalianbody created by any means.

[0006] Description of the prior art

[0007] Openings may be formed in a human or other mammalian body bynumerous means. Needles or other medical instruments may create punctureor other types of openings, for example. Moreover, electrical,ultrasound, optical instruments and the like may create openings.Gunshot and knife wounds and numerous other events may also causeopenings to be formed.

[0008] An opening in a lung is undesirable because air leaks therefromand causes the lung to collapse. However, openings in soft tissue, aswell as openings in internal organs, such as the heart, kidney, liver,etc., also require closure. Openings in bones, cartilage, ligaments, andother hard tissue must also be closed.

[0009] Many techniques have been developed for the surgical closing ofopenings. Sutures were invented long ago, for example. One importantdrawback to using sutures in some applications arises from the fact thatthe needle used to sew the suture in place typically has a diameter thatis larger than the suture. Thus, if a suture is used to close an openingin a lung, for example, air can escape from the lung in the space thatsurrounds the suture, i.e., the space has the diameter of the needle andis not fully occupied by the suture. This problem is addressed byapplying an adhesive over the suture; when the adhesive cures, theopenings around the suture are sealed. However, adhesives are difficultto apply and control and require time to cure.

[0010] Another more recently developed technique for closing openingsincludes the use of staples. The force required to apply staples mayresult in torn tissue. One solution to this problem is to apply anadhesive over the staples to seal the torn areas, just as is done inconnection with sutures.

[0011] Adhesive have been used to close other openings in the body aswell. Laparoscopic and endoscopic procedures, for example, may requiresophisticated instrumentation. In situ curing of adhesives may beproblematic depending upon the application, and may require the use ofcuring agents and other means for cross-linking free radicals to formthe required bond. The curing agent may be air, visible light,ultraviolet light, heat, laser beams, chemical compounds that requiremixing with one another, and so forth.

[0012] It would be advantageous therefore, if means for closing anopening could be found that did not rely upon adhesives and curingagents.

[0013] Numerous medical procedures and even non-medical events canresult in openings in the body that need to be sealed, as mentionedearlier. Openings must be closed not just to stop the escape of air fromthe lungs, but to also stop the escape of body fluids from other bodyparts. Sealing means for closing openings are needed to stop the flow ofblood, cerebral spinal fluid, and other fluids.

[0014] For exemplary purposes, an opening made by a biopsy needle willbe considered. In a biopsy procedure, a needle adapted to collect tissueis inserted into a suspected lesion, usually multiple times. When asufficient quantity of the lesion has been collected, it is taken to alab for analysis.

[0015] To perform the procedure, a coaxial needle is first inserted sothat its leading end is positioned near the suspected lesion. A biopsyneedle is then inserted through the coaxial needle.

[0016] The puncture opening made by the coaxial needle may close andheal naturally if the lesion is in soft tissue such as a breast.However, if a lesion is in the lung, the puncture opening made by thecoaxial needle may need to be closed quickly. The use of sutures oradhesives, or sutures and adhesives, are well-known as alreadymentioned, but such techniques have limitations.

[0017] What is needed, then, is an apparatus for closing an opening in alung or other vascular organ as well as in soft or hard tissue. Theneeded apparatus should close an opening quickly but should not causeproblems of the type associated with adhesives.

[0018] Physicians often have a need to re-visit a surgical proceduresite to monitor a patient's recovery. However, the sutures and adhesivesnow in use include no means for helping a physician find the surgicalsite when a follow-up look is desired.

[0019] Thus there is also a need for a means that would enable a surgeonto locate a surgical site in the days, weeks, or months following asurgical procedure.

[0020] However, in view of the prior art considered as a whole at thetime the present invention was made, it was not obvious to those ofordinary skill in the pertinent art how the identified needs could befulfilled.

Summary of Invention

[0021] The long-standing but heretofore unfulfilled need for a methodand apparatus for sealing openings made by medical or non-medicalprocedures in a mammalian body is now met by a new, useful, andnonobvious invention.

[0022] A first embodiment of the invention includes a plug formed of apreselected bioabsorbable material that expands in response to apredetermined stimulus. The plug is sized to fit within the openingprior to application of the predetermined stimulus to the dehydratedplug. The plug expands upon application of the predetermined stimulusthereto until the plug seals the opening. In this way, the plug, whenexpanded, prevents flow of liquid or gaseous fluid through the opening.The plug is gradually bioabsorbed as natural processes heal the opening.The preselected bioabsorbable material is a dehydrated hydrogel and thepredetermined stimulus is moisture that is naturally present in themammalian body.

[0023] The plug may have a solid, cylindrical configuration prior toapplication of the predetermined stimulus thereto so that the plug isadapted to fit into a lumen of a needle to facilitate introduction ofthe plug into the opening.

[0024] If the plug is to be employed as a scaffold for tissueregeneration, it may be provided in forms more suitable for thatpurpose. For example, it may have a corkscrew configuration at one end.It may also be designed to provide a mechanical anchor as well, having aleading end that expands radially outwardly after placement to preventunintended outward migration of the plug.

[0025] The plug is impregnated with a contrasting agent to facilitatedetection of the plug by imaging means selected from the group ofimaging means consisting of magnetic resonance imaging, ultrasound,Doppler, and roentgenological means including x-ray, CT scan,mammography, and fluoroscopy.

[0026] Alternatively, the plug includes a radioactive substancedetectable by a radiation detecting means including a gamma counter anda scintillation counter. In another alternative, the plug includes atransmitting means adapted to transmit signals in the electromagneticspectrum that are detectable by receivers adapted to receive signals inthe electromagnetic spectrum.

[0027] The plug is adapted to be slideably disposed in a lumen of aneedle. A plug displacement means is adapted to abuttingly engage andslidingly displace the plug within the lumen to a preselected locationnear a distal end of the lumen. Withdrawal of the needle coupled withmaintaining the plug displacement means at said preselected locationduring the withdrawal results in placement of the plug at thepreselected location. Withdrawal of the plug displacement means does notcause displacement of the plug.

[0028] The novel material also has utility in promoting angiogenesis ina mammalian heart. A cavity or bore is formed in a heart and growthfactor means is introduced into the bore. A bioabsorbable plug thatexpands in response to a predetermined stimulus then plugs the bore. Thepredetermined stimulus is applied to the bioabsorbable plug so that thebioabsorbable plug expands and seals the growth factor means within thebore.

[0029] The novel plug has further utility as a means for preventing lossof spinal fluid from the thecal sac. An opening is formed at apreselected site in the thecal sac by a biopsy needle introduced to thepreselected site through a coaxial needle. The biopsy needle iswithdrawn from the preselected site after the opening has been formed. Adelivery catheter having a dehydrated, bioabsorbable plug formed of apreselected material that expands in response to a predeterminedstimulus positioned in its lumen is then introduced through the coaxialneedle to the preselected site. The dehydrated, bioabsorbable plug ispushed from the lumen of the catheter into the opening and said catheteris withdrawn from the preselected site. The bioabsorbable plug expandsupon being hydrated by natural fluids present at the preselected site.The expansion holds the plug in place and further serves to preventleakage of spinal fluid from the opening.

[0030] The novel material is not limited to plugs. For example, it mayalso be formed into a cylindrical member that slideably receives a plug.Such a cylindrical member and a plug may be used with one another toprovide a means for sealing an incision in an artery. More particularly,a guide wire is inserted through the incision and a lumen of anintroducer sheath is placed in receiving relation to the guide wire sothat a leading end of the introducer sheath is guided to the incision bythe guide wire. The leading end of the introducer sheath is positionedinto abutting and surrounding relation to the incision. A dehydrated,bioabsorbable tube formed of a preselected material that expands inresponse to a predetermined stimulus is pushed from a lumen of theintroducer sheath so that a leading end of the dehydrated, bioabsorbabletube is disposed in abutting and surrounding relation to the incision.The guide wire and the introducer sheath are then withdrawn from theartery. The leading end of a delivery catheter having an externaldiameter less than an internal diameter of the dehydrated, bioabsorbabletube is then introduced into the lumen of the dehydrated, bioabsorbabletube. A dehydrated, bioabsorbable plug formed of a preselected materialthat expands in response to a predetermined stimulus is positioned in alumen of the delivery catheter and is pushed from said lumen into thelumen of the dehydrated, bioabsorbable tube. The delivery catheter iswithdrawn and the dehydrated, bioabsorbable plug expands within thelumen of the dehydrated, bioabsorbable tube when contacted by naturalmoisture within the blood flowing through the artery. The dehydrated,bioabsorbable tube expands when contacted by the natural moisture withinthe blood and by natural moisture within tissue that surrounds theartery.

[0031] In another embodiment, an elongate suture is formed of apreselected bioabsorbable material that expands in response to apredetermined stimulus. The elongate suture is adapted to be pulled by aneedle so that the elongate suture is used to sew closed the opening.The elongate suture has a diameter slightly less than a diameter of theneedle, there being a clearance space about the elongate suture equal indiameter to the diameter of the needle less the diameter of the elongatesuture. The elongate suture expands upon application of thepredetermined stimulus thereto until the elongate suture seals theclearance space. The elongate suture, when expanded, prevents flow ofliquid or gaseous fluid through the clearance space and is graduallybioabsorbed as the opening is healed by natural processes. Thepreselected bioabsorbable material is a hydrogel and the predeterminedstimulus is moisture that is naturally present in a mammalian body. Theelongate suture may be impregnated with a contrasting agent tofacilitate its detection by imaging means selected from the group ofimaging means consisting of magnetic resonance imaging, ultrasound,Doppler, and roentgenological means including x-ray, CT scan,mammography, and fluoroscopy. The elongate suture may include aradioactive substance detectable by a radiation detecting meansincluding a gamma counter and a scintillation counter. Alternatively, itmay include a transmitting means adapted to transmit signals in theelectromagnetic spectrum that are detectable by receivers adapted toreceive signals in the electromagnetic spectrum. Moreover, the elongatesuture may be hollow and filled with a gaseous fluid.

[0032] A conventional suture, both bioabsorbable and nonbioabsorbable,may be coated with a material that expands in response to apredetermined stimulus and used in the same way as the suture madeentirely of the novel material. This type of coating also provides alubricious surface having a low coefficient of friction to minimizetrauma during the suturing process.

[0033] A rigid medical staple of the type used in anastomosis of organsmay also be coated with a preselected bioabsorbable material thatexpands in response to a predetermined stimulus to fill the openingsmade by the stapling procedure.

[0034] An important object of this invention is to provide a means forsealing openings in a mammalian body quickly and in the absence ofconventional sutures, staples, and adhesives.

[0035] Another object is to provide a bioabsorbable means for sealingsuch openings.

[0036] Another major object is to provide a marking means that enables aphysician to easily find a surgical site for follow-up purposes.

[0037] These and other important objects, advantages, and features ofthe invention will become clear as this description proceeds.

[0038] The invention accordingly comprises the features of construction,combination of elements, and arrangement of parts that will beexemplified in the description set forth hereinafter and the scope ofthe invention will be indicated in the claims.

Brief Description of Drawings

[0039] For a fuller understanding of the nature and objects of theinvention, reference should be made to the following detaileddescription, taken in connection with the accompanying diagrammaticdrawings, in which:

[0040]Fig. 1 is a side elevational view of a biopsy needle taking asample from a lesion in a lung or any other soft tissue;

[0041]Fig. 2 is a view depicting the positioning of a bioabsorbable plugin the coaxial needle of Fig. 1;

[0042]Fig. 3 is a view like that of Fig. 2, but after the coaxial needlehas been withdrawn, leaving the bioabsorbable plug in sealing relationto a puncture wound;

[0043]Fig. 4 is a view like that of Fig. 3, but depicting the plug inits enlarged configuration;

[0044]Fig. 5 is a view of an alternative embodiment where thebioabsorbable seal is positioned on an inside surface of a lung;

[0045]Fig. 6 is a view of an alternative embodiment where thebioabsorbable seal is positioned on an outside surface of a lung;

[0046]Fig. 7A is a longitudinal sectional view of a tubular plug;

[0047]Fig. 7B is a longitudinal sectional view of a plug having anenlarged leading end;

[0048]Fig. 7C is a longitudinal sectional view of a plug that may beused as a "scaffold"for therapeutic drugs or the like;

[0049]Fig. 7D is a longitudinal sectional view of another plugconfiguration having utility as a scaffold;

[0050]Fig. 7E is a longitudinal sectional view of another plugconfiguration having utility as a scaffold;

[0051]Fig. 7F is a longitudinal sectional view of another plugconfiguration having utility as a scaffold;

[0052]Fig. 7G is a longitudinal sectional view of another plugconfiguration having utility as a scaffold;

[0053]Fig. 7H is a view of an alternative, hollow bioabsorbable plug;

[0054]Fig. 8A is a view of a bioabsorbable suture in isolation;

[0055]Fig. 8B is a view of a bioabsorbable suture in use to close anincision;

[0056]Fig. 9A is a view depicting the formation of a blind bore or corein the myocardium of a mammalian heart;

[0057]Fig. 9B is a view depicting the injection of growth factors intothe blind bore;

[0058]Fig. 9C is a view depicting the delivery of a bioabsorbable sealto the biopsy site;

[0059]Fig. 9D depicts the bioabsorbable seal in sealing relation to thegrowth factor;

[0060]Fig. 9E depicts a plurality of blind bores filled with growthfactor and sealed with the bioabsorbable plugs of this invention;

[0061]Fig. 9F depicts the formation of a cavity in the interior surfaceof the myocardium;

[0062]Fig. 9G depicts the plugging of the cavity of Fig. 9F with thenovel bioabsorbable seal so that growth factor is sealed therein;

[0063]Fig. 10A is a diagrammatic view depicting puncturing of the thecalsac to withdraw cerebral spinal fluid;

[0064]Fig. 10B is a similar view depicting the delivery of a dehydratedplug to the puncture site;

[0065]Fig. 10C depicts the hydrated plug in closing relation to thepuncture formed in the thecal sac;

[0066]Fig. 11A is the first view in a series of animations depicting thefirst step of a method where an embodiment of the novel plug is used toseal an incision formed in an artery;

[0067]Fig. 11B is the second view in said series of animations;

[0068]Fig. 11C is the third view in said series of animations;

[0069]Fig. 11D is the fourth view in said series of animations;

[0070]Fig. 11E is the fifth and final view in said series of animations;

[0071]Fig. 12A is a front elevational view of a staple coated with thenovel expandable and bioabsorbable material;

[0072]Fig. 12B is a front elevational view of the staple of Fig. 12Aafter activation;

[0073]Fig. 12C is a sectional view depicting tissue on opposite sides ofan incision joined to one another by the novel staple;

[0074]Fig. 13A is a diagrammatic view of a cavity formed in tissue beingfilled with the novel dehydrated bioabsorbable polymers of thisinvention;

[0075]Fig. 13B is a diagrammatic view depicting the cavity filled by theexpanded polymers;

[0076]Fig. 14A is a diagrammatic view of an aneurysm being filled withthe novel dehydrated bioabsorbable polymers of this invention;

[0077]Fig. 14B is a diagrammatic view depicting the aneurysm filled bythe expanded polymers;

[0078]Fig. 15A diagrammatically depicts a hole in a septum of amammalian heart;

[0079]Fig. 15B is the first diagram in a four series animation depictingthe novel steps for sealing said hole;Fig.

[0080] 15C is the second diagram in said series of animations;

[0081]Fig. 15D is the third diagram of said series; and

[0082]Fig. 15E is the fourth diagram of said series.

Detailed Description

[0083] Referring to Fig. 1, it will there be seen that the referencenumeral 10 denotes a biopsy site as a whole. Openings in a mammalianbody may be formed by numerous other medical procedures and non-medicalevents as mentioned earlier. A biopsy procedure is explained just forexemplary purposes.

[0084] A biopsy needle 12 is ensleeved within lumen 13 of coaxial needle14 when taking biopsy samples from lesion 16 because multiple entriesand withdrawals of biopsy needle 12 are normally required. In theabsence of coaxial needle 14, biopsy needle 12 would have to makemultiple punctures of the patient's skin and lung during a biopsyprocedure. Although coaxial needle 14 has a slightly larger diameterthan biopsy needle 12, the trauma caused by one insertion of saidcoaxial needle is less than that of multiple biopsy needle insertions.

[0085] In the example if Fig. 1, the patient's skin is denoted 18 andthe surface of the patient's lung is denoted 20. It should beunderstood, however, that the utility of this invention is notrestricted to sealing openings formed in lungs by biopsy procedures butincludes the sealing of openings formed by any means in the heart,brain, liver, kidneys, and even in hard tissue such as bone, cartilage,and the like.

[0086] When a sufficient amount of biopsy samples have been taken,biopsy needle 12 is withdrawn from coaxial needle 14.

[0087] As depicted in Fig. 2, a pusher assembly that includes a circulardisc 24 and a rod 26 then slidingly introduces dehydrated plug 22 intolumen 13 of coaxial needle 14. In this first-described embodiment, plug22 is of solid cylindrical construction, is about 2.5 cm in length, andis positioned approximately as shown in Fig. 2, i.e., a small extent ofthe plug is external to surface 20 of the lung and a larger extentthereof is inside the lung. This particular positioning is not criticaland is depicted just to indicate that plug 22 is preferably a relativelylong cylindrical plug, in this particular application, so that it isrelatively easy to position in sealing relation to the puncture opening.The elongate extent of plug 22 provides a generous margin of error.

[0088]Fig. 3 depicts biopsy site 10 after withdrawal of coaxial needle14. Pusher disc 24 and rod 26 (Fig. 2) are held in place when coaxialtube 14 is withdrawn to ensure that plug 22 does not move. After coaxialtube 14 is fully withdrawn, pusher disc 24 and rod 26 are withdrawn toproduce the view of Fig. 3.

[0089] Plug 22 is formed of a material that expands upon contact with astimulant such as water, blood, air, visible light or otherelectromagnetic radiation such as a laser beam, a preselected chemical,and so on. In a preferred embodiment, the stimulant is moisture which isnaturally present on the surface of a patient's lungs or other softtissue, internal organs, or the like.

[0090]Fig. 4 depicts plug 22 shortly after its installation. It has beenin contact with moisture, or other predetermined stimulant, for a fewmoments and the expandable material has expanded. The expansioneffectively seals the peripheral edge of the puncture opening andprevents air from escaping the lungs. In other applications, the plug isused to stop bleeding or other liquid fluid flow from the liver, heart,thecal sac, etc.

[0091] An alternative embodiment is depicted in Fig. 5. In thisembodiment, bioabsorbable element 22a is releasably secured to thedistal end of rod 28. Element 22a is disk-shaped, having lesslongitudinal extent than bioabsorbable plug 22 of the first embodiment.Plug 22a has an unexpanded diameter that is preferably slightly greaterthan that of plug 22 so that it deploys to a diameter that is at leastslightly greater than the diameter of the puncture wound when coaxialrod 14, not shown in Fig. 5, is retracted. Rod 28 is then retracted andseparated from plug 22a when said plug 22a is firmly positioned insealing relation to the inner wall of lung 20.

[0092] There are numerous means for interconnecting rod 28 and plug 22asuch that said rod may be separated from plug 22a when said plug isfirmly positioned in sealing relation to the puncture opening. Anadhesive having a predetermined strength may be used, for example, andseparation would occur upon applying a torque to rod 28 about itslongitudinal axis.

[0093] Another alternative embodiment is depicted in Fig. 6. Thisembodiment is much like the embodiment of Fig. 5 except that plug 22a ispositioned in firmly sealing relation to the puncture opening on theexterior surface of the lung prior to separation of plug 22a and rod 28.

[0094]Figs. 7A-H depict a few of the possible variations of plug 22. Allof these plugs are in a dehydrated condition when positioned withinlumen 13 of coaxial needle 14 and are expanded by contact with thebody's natural moisture or by other means as mentioned earlier uponbeing pushed from said lumen by the earlier-mentioned pusher assembly.

[0095] In Fig. 7A, plug 22 is of tubular construction. This plug wouldnot have utility in sealing an opening in a lung, obviously.

[0096] Plug 22 of Fig. 7B has an enlarged anchor member 22b at itsleading end. Anchor member 22b is compressed when plug is within lumen13 and expands at least to some extent under its own bias upon emergencefrom said coaxial needle.

[0097] Plug 22 of Fig. 7C is generally "U"-shaped when seen inlongitudinal cross-section as in said Fig. 7C.

[0098] Plug 22 of Fig. 7D has a structure similar to that of Fig. 7C butfurther includes an outwardly turned flange 22c at its leading end.Flange 22c performs the same function as anchor member 22b of Fig. 7B,i.e. it prevents longitudinal travel of the plug in a direction towardthe surface of the body, it being understood that the flange or anchormember is positioned in abutting relation to an interior side of anopening formed in an organ or other tissue.

[0099] Plug 22 of Fig. 7E has an irregular or corkscrew leading end.Fig. 7F depicts a plug having a leading end in the configuration of atapered corkscrew. Plug 22 of Fig. 7G includes a medal part of irregularconfiguration flanked by a leading and a trailing end of solidcylindrical configuration.

[0100] Significantly, the embodiments of Figs. 7C-G enable plug 22 toserve as a "scaffold"upon which may be deposited growth hormone, stemcells, therapeutic drugs or any type, and so on. The increased surfacearea provides means for holding such therapeutic elements. Plug 22 or22a may have a solid or hollow construction. The embodiment 22b of Fig.7H is hollow and is filled with a gaseous fluid either just before orjust after it is positioned in sealing relation to a puncture opening.The gaseous fluid is introduced into the hollow interior of plug 22bthrough rod 30, said rod being in fluid communication with balloon-likeneck 22c of plug 22b. Plug 22b is expanded by gas introduction until itfirmly seals the opening. Neck 22c is then sealed by any suitable means.

[0101] Alternatively, plug 22b is filled with a gaseous fluid prior toits use and neck 22c is sealed prior to introduction of the plug.

[0102] It should be understood that the lung is not the only internalorgan of the body that may be punctured by a needle or other medical ornon-medical device and require sealing. Openings formed in any vascularorgans such as the kidneys, the liver, the heart, the brain, and thestomach, for example, may be sealed with the novel apparatus. Nor is theinvention limited to the sealing of vascular organs. For example, it maybe used to seal an opening formed in the thecal sac. The novel apparatushas utility in sealing openings formed by any means in any mammaliansoft or hard tissue.

[0103] It may also be used to seal surgical sites of the type createdduring arthroscopic, endoscopic, or laporoscopic procedures conducted onthe knee, back, and neck, for example. The diameter of the expandable,bioabsorbable plug would be increased as required to fill the trocar orother device that performs the role of a coaxial needle.

[0104] As an additional example, the novel plug may be employed to sealan incision of a femoral artery.

[0105] Plug 22 is formed of a bioabsorbable material so that it isbioabsorbed by the body as the opening heals. Since people heal atdifferent rates, a bioabsorbable material should be selected so that itis fully bioabsorbed in a period of time such as a few weeks to a fewmonths.

[0106] Examples of suitable bioabsorbable materials that expand whencontacted by water include hydrogels, collagen, polysalactic acid, andany other suitable hydrophilic agents.

[0107] Examples of polymers that swell in the presence of aqueous fluidssuch as biological fluids will now be disclosed. Virtually all of thefollowing polymers are hydrogels. Synthetic hydrogels can be preparedfrom the following classes of polymers and these are generallyconsidered to be non-biodegradable:poly(hydroxyalkyl methylacrylates)such as poly(glyceryl methacrylate)poly(acrylamide) andpoly(methacrylamide) and derivativespoly(N-vinyl-2-pyrrolidone)anionicand cationic hydrogelspoly(vinyl alcohol)poly(ethylene glycol)diacrylate and derivatives from block copolymers composed ofpoly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) andpoly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) blocks,respectively; All of the above can be cross-linked with agents such asethylene glycol dimethacrylate or methylene-bis-acrylamide.

[0108] Biodegradable synthetic hydrogels can be prepared from polymerssuch as those listed above by incorporating one or more of the followingmonomers:Glycolide, Lactide, e-Caprolactone, p-Dioxanone andTrimethylene CarbonateIn addition, biodegradable hydrogels can be basedon natural products such as the following:Polypeptides such gelatinwhich may be cross-linked with formaldehyde or glutaraldehyde andvarious other dialdehydes.

[0109] Modified chitin hydrogels, which may be prepared from partiallyN-deacetylated chitin which, may then be cross-linked with agents suchas glutaraldehyde.

[0110] Dextran, a polysaccharide, can be derivatized with groups such as3-acryloyl-2-hydroxypropyl esters and subsequently cross-linked by freeradical copolymerization with N',N'-methylenebisacrylamide.

[0111] Starch may be similarly derivatized or using glycidyl acrylatefollowed by free radical cross-linking as described above.

[0112] The novel plug is also treated so that it is visible underfluoroscopy, ultrasound, X-ray, magnetic resonance imaging, computedaxial tomography (CAT) scanning, and other imaging techniques.Accordingly, it may contain or be impregnated with a contrast solutioncontaining radium, iodine, beryllium, or other contrasting agent.

[0113] The bioabsorbable material of this invention could also befabricated in a thread-like form and used as a suture material.Alternatively, after a suture has been made using conventional suturematerial, the bioabsorbable material could be topically applied to thesutured area to help seal the punctures made by the suture.

[0114]Fig. 8A depicts an elongate thread of suture material 32 formed ofthe novel dehydrated hydrogel material of this invention and Fig. 8Bdepicts said suture material 32 in use to close an incision formed intissue 33.

[0115] In a first suture embodiment, suture material 32 is formedentirely of the dehydrated hydrogels of this invention. When suturematerial 32 comes into contact with tissue, the natural moisture withinthe tissue causes material 32 to expand and seal the hole created by theneedle, it being understood that the needle has a diameter greater thanthat of the suture material 32. The body heals as the bioabsorbablesuture is absorbed and no suture material remains after the holes havecompletely closed as a result of natural healing.

[0116] In a second embodiment, regular PGA/PLA sutures or evennon-bioabsorbable sutures are coated with the novel suture material,i.e., extensible type polymers such as hydrogel that have beendehydrated. Figs. 8A and 8B should also be interpreted as depicting thissecond embodiment. The coating expands upon contact with the moisture inthe tissue. The non-bioabsorbable suture underlying the bioabsorbablesuture material will remain, of course, after the bioabsorbable materialhas been absorbed but the body's natural healing process will havesealed the holes around the suture. Where a regular PGA/PLA suture iscoated, it too will bioabsorb as the coating is bioabsorbed.

[0117] Advantageously, the body's natural moisture, in mostapplications, will cause the suture or the suture coating to expand tofill the space around it created by the larger diameter of the needle.This eliminates the need to apply an adhesive over the sutures and thuseliminates the step of curing the adhesive.

[0118]Figs. 9A 9G disclose how the novel plugs can be used to fillcavities formed in heart tissue to promote angiogenesis in heartpatients. Growth factor, stem cells, or the like are placed in thecavities or blind bores and sealed therein by means of the novel plugsdisclosed herein. In Fig. 9A, coaxial needle 40 is depicted inpenetrating relation to epicardium 42 and myocardium 44. Endocardium 46is not penetrated to avoid puncturing left ventricle 48 of heart 50 inthis particular example. Biopsy needle 52 is inserted through the lumenof coaxial needle 40 to remove a core of tissue from myocardium 44. Thiscreates a blind bore in myocardium 44.

[0119] Biopsy needle 52 is then removed from the lumen of coaxial needle40 and a delivery sheath 54 is inserted into the lumen of said coaxialneedle as depicted in Fig. 9B. Growth factor 55 such as vascularendothelial growth factor, stem cells, or the like are pushed into theblind bore from the lumen of delivery sheath 54 by plunger 56.

[0120] Plunger 56 is then momentarily withdrawn from the lumen ofdelivery sheath 54 and a dehydrated bioabsorbable plug 22d is insertedinto said lumen. Plunger 56 is then retrieved to push plug 22d intosealing relation to the blind bore as indicated in Fig. 9C.

[0121]Fig. 9D depicts plug 22d in said sealing relation. Growth factor55 deposited into the bottom of the blind bore is sealed therein bybioabsorbable plug 22d. Plug 22d is hydrated by the natural moisture orbody fluids of the myocardium and in Fig. 9D has expanded to tightlyseal the blind bore so that growth factor 55 cannot leak therefrom.

[0122]Fig. 9E depicts multiple blind bore sites filled with growthfactor 55 and sealed by plugs 22d. Growth factor 55 promotesangiogenesis so that newly formed blood vessels can perform the functionof dead or damaged blood vessels throughout the damaged region of theheart. Exterior surface 23 of each plug 22d is hydrophillic so thatpericardium tissue does not attach to the biopsied site.

[0123] The blind bores or cavities can also be formed in the interiorsurface of the myocardium as depicted in Figs. 9F and 9G. Cavity 53 inFig. 9F is formed in endocardium 46 by a biopsy gun or other suitableinstrument and filled with growth factor. Epicardium 42 is not puncturedin this embodiment. Dehydrated bioabsorbable plug 22d is then slid intosealing relation to cavity 53 by a suitable plunger means to create thestructure seen in Fig. 9G. Damaged heart tissue in the vicinity ofcavity 53 is then regenerated by neovascularization. Multiple cavities53 can be formed in the interior side of myocardium 44 as needed.

[0124]Fig. 10A depicts coaxial needle 40 that receives the needle ofsyringe 58 used to withdraw spinal fluid 59 from spinal cord 60. Neckmuscle is denoted 61.

[0125] Syringe 58 is then withdrawn and as indicated in Fig. 10B,dehydrated bioabsorbable plug 22d is pushed from the lumen of deliverycatheter 54 by plunger 56 into sealing relation with the opening made bythe needle of syringe 58.

[0126]Fig. 10C depicts bioabsorbable plug 22d in sealing relation to theopening made by said needle. Said plug 22d is in its expandedconfiguration due to the natural moisture provided by spinal fluid 59,spinal cord 60, and neck muscles 61.

[0127]Figs. 11A 11E depict how a plug of this invention may be employedto seal an incision made in an artery.

[0128] In Fig. 11A, guide wire 70 is depicted inserted into femoral orother artery 72 through incision 71, which may be made for diagnostic orintervention purposes. After the primary diagnostic or interventionprocedures have been performed, the instruments used are removed butguide wire 70 is left in position so that it may be used as follows.Leading end 74a of introducer sheath 74 is positioned in abuttingrelation to artery 72 and in surrounding relation to incision 71.Reference numeral 73 denotes fat and 75 is the skin surface.

[0129] A dehydrated bioabsorbable material 22e in the form of a tube isthen introduced through lumen 76 of introducer sheath 74 so that itsleading end also abuts artery 72 in surrounding relation to incision 71,as depicted in Fig. 11B.

[0130] Introducer sheath 74 is then withdrawn, leaving tube 22e inencircling relation to incision 71 as depicted in Fig. 11C.

[0131] Guide wire 70 is then removed. As indicated in Fig. 11D, anintroducer sheath 80 having a smaller external diameter than introducersheath 74 of Fig. 11B, is employed to position dehydrated plug 22f inplugging relation to tube 22e. Specifically, plug 22f is disposed inlumen 81of introducer sheath 80 and the leading end of said introducersheath 80 is slideably inserted into the trailing end of tube 22e asdepicted. Plunger 82 is then employed to push plug 22f into tube 22e.Note that plug 22f need not abut incision 71 to accomplish its sealingfunction.

[0132]Fig. 11E depicts tube 22e and plug 22f after withdrawal ofintroducer sheath 80 and plunger 82. Both tube 22e and plug 22f are nowhydrated by the natural moisture of the body. Accordingly, both haveexpanded and are held in place by fat 23 and by each other. Moreover,the moisture content of the blood flowing through the artery also servesto cause the expansion of tube 22e and plug 22f. Incision 71 will healgradually and tube 22e and plug 22f will be bioabsorbed over time. Thetrailing end of tube 22e that projects upwardly from the surface of skin75 may be trimmed so that it is flush with said skin or slightlycountersunk with relation thereto.

[0133]Figs. 12A-C depict the use of the novel material in the context ofstaples. Conventional, nonbioabsorbable staples are often used to closeincisions. The staples of this embodiment are used in end-end andend-side anastomosis of organs such as the lung, the bowel, and thelike. Fig. 12A depicts a staple 90 before it has been used and Fig. 12Bdepicts said staple 90 after activation. Fig. 12C depicts said staplewhen holding together two pieces of tissue 91 and 92 separated byincision 93. This embodiment requires the use of the novel material as acoating over a conventional staple because the conventional stapleprovides the required stiffness to enable the staple to punch throughtissue layers 91, 92. The coating then expands to seal the holes createdby the staple and the holes heal gradually as the bioabsorbable coatingis bioabsorbed.

[0134] From the foregoing, it is apparent that the novel method includesthe steps of sealing an opening of the type made by a needle or othermedical or non-medical instrument by providing a plug formed of abioabsorbable material that expands in response to a predeterminedstimulus. The plug may be positioned within the lumen of a needle, adelivery sheath, or the like, and pushed therefrom by a suitable pushingmeans or it may installed by any other suitable method. The particularmethod of installation depends upon the type of opening being pluggedand the particular method of application is not critical to thisinvention. In an exemplary embodiment involving a needle, the plug isslidingly displaced by a plunger means to a preselected location near adistal end of the lumen of the needle. Withdrawal of the needle coupledwith maintaining the plug at the preselected location results inplacement of the plug at the preselected location. The predeterminedstimulus is then applied to cause expansion of the plug and sealing ofthe opening made by the needle.

[0135] Where the novel material is formed into a thread-like form foruse as a suture material, or as a coating for conventional suturematerial which or may not be bioabsorbable, the novel method includesthe steps of sewing an opening in accordance with acceptable medicalprocedure. In most applications, the natural moisture of the body willthen cause the suture or the coating to expand radially and to therebyfill the space around it created by the larger diameter of the needle.Where insufficient moisture is present, it can simply be brushed orsprayed on in the form of a saline solution, for example. As mentionedearlier, other activating agents other than moisture are also within thescope of this invention.

[0136] Where the novel material is used as a coating for conventionalstaples, the novel method includes the step of using the coated staplesin accordance with acceptable medical practice. The coating expands tofill openings or holes created by the staples and said coating isbioabsorbed as the opening heals.

[0137] The novel expandable polymers also have utility in fillingcavities in tissue. For example, as depicted in Fig. 13A, a cavity 100may be formed in tissue 102 such as a liver or other organ when a tumoror lesion is removed. Catheter 104 is introduced to the site and aplurality of dehydrated plugs 22 of the novel material are pushed intocavity 100. As depicted in Fig. 13B, plugs 22 expand upon contact withnaturally present moisture and fill the cavity. This prevents infectionsor other complications that may arise if the cavity is left unfilled.

[0138] As another example, novels plugs 22 may also be used to fill aspace created by an aneurysm. In Fig. 14A, aneurysm 106 has formed apocket adjacent artery 108. Catheter 110 is introduced into aneurysm 106through artery 108 and a plurality of the novel plugs 22 in dehydratedcondition are pushed into the aneurysm. As indicated in Fig. 14B,available natural moisture causes expansion of plugs 22 and the cavityleft behind by the aneurysm is filled.

[0139] It is therefore understood that the novel plugs have utility notjust in applications where an opening has been formed in the surface oftissue, but in filling cavities or other pockets within tissue as well,without regard to the cause of the cavity or pocket.

[0140] It should also be understood that there are applications wherewaiting for natural body fluids to activate the dehydrated plug or plugsmay be contraindicated. In those applications, saline or other suitablesource of moisture is injected into the lumen of the needle or catheterof other plug-delivery device before the plug is pushed therefrom anddeposited into an opening or cavity. In this way, hydration of the plugbegins while the plug is still undeployed so that the time required forfull expansion after the plug has left the delivery device is reduced oreven eliminated.

[0141] Yet another application for the novel expandable, bioabsorbablematerials is in the patching of a hole or holes in a mammalian heart. Inthe example of Fig. 15A, a hole 120 in septum 122 unacceptably providesfluid communication between right atrium 124 and left atrium 126. Asindicated in Fig. 15B, guide wire 70 is fed through femoral vein 128 sothat the distal free end of guide wire 70 passes though hole 120 inseptum 122 and enters into left atrium 126. A delivery catheter orsheath 130 is then fed over the guide wire until the distal free end ofthe sheath is also positioned within left atrium 126.

[0142] Guide wire 70 is then removed as indicated in Fig. 15C. Plug 22is then pushed from the lumen of sheath 130, by holding it in place witha plunger while slightly withdrawing sheath 130, until the distal freeend of the plug is positioned within the left atrium. Plug 22 is allowedto expand upon contact with natural moisture in the heart. It may alsobe pre-hydrated by injecting saline or other suitable solution into thelumen of sheath 130 prior to deployment of plug 22 so that the expansiontime is reduced or eliminated. The expansion of plug 22 in left atrium126 provides an anchoring means so that sheath 130 can be slowlywithdrawn, leaving plug 22 deployed in opening 120.

[0143] Sheath 130 is then withdrawn further as depicted in Fig. 15D sothat plug 22 begins expanding in right atrium 124. Sheath 130 is thenfully withdrawn as depicted in Fig. 15E. Plug 22 is now fully expandedand hole 120 is closed so that the left and right atriums are no longerin fluid communication with one another.

[0144] Plug 22 is coated or impregnated with a contrasting agent tofacilitate its viewing and hence accurate placement when employingvarious imaging techniques, as in the embodiments described above.

[0145] A plug used to seal an opening in a heart is preferably formed ofa material that is bioabsorbed very slowly over a long period of time.Plug 22 may also be impregnated with a growth factor or othertherapeutic agents to promote healing.

[0146] It will thus be seen that the objects set forth above, and thosemade apparent from the foregoing description, are efficiently attained.Since certain changes may be made in the above construction withoutdeparting from the scope of the invention, it is intended that allmatters contained in the foregoing description or shown in theaccompanying drawings shall be interpreted as illustrative and not in alimiting sense.

[0147] It is also to be understood that the following claims areintended to cover all of the generic and specific features of theinvention herein described, and all statements of the scope of theinvention that, as a matter of language, might be said to falltherebetween.

[0148] Now that the invention has been described,

Claims
 1. An apparatus for sealing an opening made by any means in amammalian body, comprising: an elongate suture formed of a preselecteddehydrated polymer material that expands in response to a predeterminedstimulus; said elongate suture adapted to be pulled by a needle so thatsaid elongate suture is used to sew closed said opening; said elongatesuture having a diameter slightly less than a diameter of said needle,there being a clearance space about said elongate suture equal indiameter to said diameter of said needle less the diameter of saidelongate suture; said elongate suture expanding upon application of saidpredetermined stimulus thereto until said elongate suture seals saidclearance space; whereby said elongate suture, when expanded, preventsflow of liquid or gaseous fluid through said clearance space.
 2. Theapparatus of claim 1, wherein said predetermined stimulus is moisturethat is naturally present in said mammalian body.
 3. The apparatus ofclaim 1, wherein said preselected dehydrated polymer material is formedof a bioabsorbable polymer so that said elongate suture is graduallybioabsorbed as said opening is healed by natural processes.
 4. Theapparatus of claim 3, wherein said bioabsorbable polymer is abioabsorbable hydrogel material.
 5. The apparatus of claim 4, whereinsaid bioabsorbable hydrogel material is selected from the groupconsisting of polypeptides cross-linked with a compound selected fromthe group consisting of formaldehyde, glutaraldehyde, and dialdehydes.6. The apparatus of claim 4, wherein said bioabsorbable polymer isimpregnated with a therapeutic substance to provide therapy as saidbioabsorbable polymer is bioabsorbed.
 7. The apparatus of claim 1,wherein said preselected dehydrated polymer material is impregnated witha contrasting agent to facilitate detection of said preselecteddehydrated polymer by imaging means selected from the group of imagingmeans consisting of magnetic resonance imaging, ultrasound, Doppler, androentgenological means including x-ray, CT scan, mammography, andfluoroscopy.